Scoping review and expert-based consensus recommendations for assessment and management of psychogenic non-epileptic (functional) seizures (PNES) in children: A report from the Pediatric Psychiatric Issues Task Force of the International League Against Epilepsy.

Limited guidance exists regarding the assessment and management of psychogenic non-epileptic seizures (PNES) in children. Our aim was to develop consensus-based recommendations to fill this gap. The members of the International League Against Epilepsy (ILAE) Task Force on Pediatric Psychiatric Issues conducted a scoping review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SR) standards. This was supplemented with a Delphi process sent to pediatric PNES experts. Consensus was defined as ≥80% agreement. The systematic search identified 77 studies, the majority (55%) of which were retrospective (only one randomized clinical trial). The primary means of PNES identification was video electroencephalography (vEEG) in 84% of studies. Better outcome was associated with access to counseling/psychological intervention. Children with PNES have more frequent psychiatric disorders than controls. The Delphi resulted in 22 recommendations: Assessment-There was consensus on the importance of (1) taking a comprehensive developmental history; (2) obtaining a description of the events; (3) asking about potential stressors; (4) the need to use vEEG if available parent, self, and school reports and video recordings can contribute to a "probable" diagnosis; and (5) that invasive provocation techniques or deceit should not be employed. Management-There was consensus about the (1) need for a professional with expertise in epilepsy to remain involved for a period after PNES diagnosis; (2) provision of appropriate educational materials to the child and caregivers; and (3) that the decision on treatment modality for PNES in children should consider the child's age, cognitive ability, and family factors. Comorbidities-There was consensus that all children with PNES should be screened for mental health and neurodevelopmental difficulties. Recommendations to facilitate the assessment and management of PNES in children were developed. Future directions to fill knowledge gaps were proposed.

The effectiveness of epilepsy educational intervention using computer game-based epilepsy educational program (Epigame) among Malaysian children with epilepsy: A prospective cohort study.

BACKGROUND: A computer game-based epilepsy educational programme (Epigame) can potentially improve the awareness, knowledge and attitude (AKA) and quality of life (QOL) of children with epilepsy (CWE). Our study among Malaysian CWE aimed to assess the: i) baseline level of epilepsy AKA and potential characteristics associated with poor levels of AKA, ii) effectiveness of Epigame in improving AKA and QOL of CWE. METHOD: Prospective cohort study on CWE age 7-18 years old with no comorbidities. Epilepsy education was delivered using Epigame. CWE completed AKA questionnaire before (time point 1 [TP1]), immediately after (TP2), 3 months (TP3) after provision of Epigame. Child self-report Health-Related Quality of Life Measurement for Children with Epilepsy (CHEQOL-25) questionnaire was completed at TP1 and TP3. RESULTS: Total of 106 CWE participated in this study (mean age of 13.3 years). Baseline (TP1) AKA was rated "very low to moderate" for awareness domain in 95.3 %, "very low to moderate" for knowledge domain in 67 %, "negative to indifferent" for attitude domain in 54.7 %, and "very poor to moderate' for total AKA score domain in 84 %. "Positive to very positive" for child attitude domain was significantly associated with parents with "positive to very positive" for attitude domain (OR 10.6, 95 % CI 3.23-34.66). "Good to excellent" for total child AKA domain was significantly associated with parents with "Good to excellent" for total AKA domain (OR 5.2, 95 % CI 1.16-15.02) and with < 2 antiseizure medication (OR 5.0, 95 % CI 1.34-18.98). The scores in the knowledge, attitude and total AKA score domains improved significantly after the introduction of Epigame at TP3. There were no significant improvements in the CHEQOL-25 scores over time except for the "Quest for Normality" subscale score (mean of score difference between TP1 and TP3 = 1.0, 95 % CI 0.19-1.81). CONCLUSION: Majority of Malaysian CWE had low levels of epilepsy AKA, particularly among parents with "negative to indifferent" for attitude domain, parents with "very poor to moderate" for total AKA domain and on polytherapy. Introduction of Epigame was effective in improving scores of the knowledge, attitude and total AKA domains, and the QOL "Quest for Normality" domain of the CHEQOL-25.

Health-related quality of life among Malaysian pediatric survivors of central nervous system tumor.

Pediatric central nervous system tumor survivors (CNSTS) experience late effects that may affect their health-related quality of life (HRQOL). The study aims: i) compare HRQOL among Malaysian CNSTS with acute lymphoblastic leukemia survivors (ALLS) and healthy children, and ii) explore factors associated with low HRQOL. We performed a comparative cross-sectional HRQOL study of 46 CNSTS aged 5-18 years and 90 ALLS (age and gender-matched) who completed treatment for >1 year, and a published cohort of healthy children. Pediatric Quality of Life Inventory (PedsQL) was used for all groups and PedsQL Cancer Module for CNSTS and ALLS. Multiple regression analysis was used to determine factors associated with low HRQOL. Mean PedsQL total scale score, physical health score and psychosocial health score of CNSTS were 69.0 (SD 20.3), 68.7 (SD 27.9) and 69.2 (SD 19.2) respectively. These scores were significantly lower in all domains particularly in teenagers compared with healthy children and ALLS. The median PedsQL Cancer Module score of CNSTS was significantly lower than ALLS in total scale, cognitive problems and communication. Physical impairment was associated with lower PedsQL scores in all 3 domains; special education placement was associated with lower PedsQL total scale and physical health scores and clinically significant internalizing behavioral difficulties score was associated with lower PedsQL psychosocial health scores. CNSTS reported lower PedsQL scores in all domains than ALLS and healthy children. Clinicians need to be vigilant of HRQOL needs among CNSTS, especially those with risk factors of special education needs, physical impairment, and internalizing behavioral difficulties.

Advance care plan discussion among parents of children with cerebral palsy.

AIM: To evaluate parental perception of advance care plan (ACP) discussions in families of Malaysian children with bilateral cerebral palsy (CP) classified in Gross Motor Function Classification System levels IV or V for (1) acceptance of the ACP discussion, (2) feedback on the usefulness of ACP discussion, and (3) exploration of possible factors related to parental acceptance of ACP. METHOD: This was a prospective pre- and post-ACP discussion questionnaire study for parents of children with bilateral CP. RESULTS: Sixty-nine patients were recruited to the study; 64 (93%) had at least one additional comorbidity. The median age was 8 years (interquartile range 5 years 1 month-11 years 6 months). Fifty-seven (82.6%) parents found the ACP discussion acceptable, and most reported positive feedback on various components of the discussion (88.4-97.1%). One-third of participants were not comfortable discussing end-of-life care plans. On multivariate analysis, parents who were comfortable discussing end-of-life care plans were more likely to find the ACP discussion acceptable (odds ratio 27.78, 95% confidence interval 2.9-265.1, p = 0.004). INTERPRETATION: Most parents of Malaysian children with bilateral CP reported the ACP discussion as both acceptable and beneficial. Parents need to be comfortable about discussing end-of-life care plans for their child to enable the ACP discussion to be an acceptable experience.

DISCUSIÓN SOBRE EL PLAN ANTICIPADO DE CUIDADOS CON PADRES DE NIÑOS CON PARÁLISIS CEREBRAL: OBJETIVO: Evaluar la percepción parental al discutir el Plan Anticipado de Cuidados (PAC) en familias de niños Malasios con parálisis cerebral bilateral (PC) niveles IV o V según el Sistema de Clasificación de la Función Motora Gruesa (GMFCS) para 1) Aceptación de la propuesta sobre el PAC, 2) opinión sobre la utilidad de discusión sobre el PAC y 3) exploración de posibles factores relacionados a la aceptación parental del PAC. MÉTODO: Se utilizó un estudio prospectivo con un cuestionario pre y post discusión sobre el PAC con padres de niños con PC bilateral. RESULTADOS: Se reclutaron sesenta y nueve pacientes para este estudio; 64 (93%) tenían como mínimo una comorbilidad adicional. La edad mediana fue 8 años (rango intercuartilo 5 años y 1 mes - 11 años y 6 meses). Cincuenta y siete (82,6%) padres hallaron aceptable la discusión sobre el PAC y la mayoría reportó una opinión positiva sobre varios componentes de la discusión (88,4 - 97,1%). Un tercio de los participantes no se sintieron bien discutiendo planes sobre cuidados del paciente terminal. Utilizando análisis multivariable, los padres que se sintieron cómodos discutiendo planes sobre cuidados del paciente terminal, con mayor probabilidad hallaron aceptable la discusión sobre el PAC (relación de probabilidades 27,78 (95%) Intervalo de confidencia 2,9-265,1, p=0,004). INTERPRETACIÓN: La mayoría de los padres de niños Malasios con PC bilateral reportaron la discusión sobre el PAC como aceptable y beneficioso. Los padres necesitan sentirse cómodos discutiendo planes sobre cuidados del paciente con múltiples comorbilidades, referidos a su hijo, a fin de permitir que la discusión sobre el PAC sea una experiencia aceptable.

Chloral hydrate as a sedating agent for neurodiagnostic procedures in children.

BACKGROUND: This is an updated version of a Cochrane Review published in 2017. Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure. OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children. SEARCH METHODS: We searched the following databases on 14 May 2020, with no language restrictions: the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 12 May 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. SELECTION CRITERIA: Randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated studies identified by the search for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals (CIs). MAIN RESULTS: We included 16 studies with a total of 2922 children. The methodological quality of the included studies was mixed. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 16 studies were at high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in small studies. Fewer children who received oral chloral hydrate had sedation failure compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study; moderate-certainty evidence). More children who received oral chloral hydrate had sedation failure after one dose compared to intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study; low-certainty evidence), but there was no clear difference after two doses (RR 3.00, 95% CI 0.33 to 27.46; 1 study; very low-certainty evidence). Children with oral chloral hydrate had more sedation failure compared with rectal sodium thiopental (RR 1.33, 95% CI 0.60 to 2.96; 1 study; moderate-certainty evidence) and music therapy (RR 17.00, 95% CI 2.37 to 122.14; 1 study; very low-certainty evidence). Sedation failure rates were similar between groups for comparisons with oral dexmedetomidine, oral hydroxyzine hydrochloride, oral midazolam and oral clonidine. Children who received oral chloral hydrate had a shorter time to adequate sedation compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study) (moderate-certainty evidence for three aforementioned outcomes), rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study), and oral clonidine (MD -37.48, 95% CI -55.97 to -18.99; 1 study) (low-certainty evidence for two aforementioned outcomes). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study; low-certainty evidence), intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study; moderate-certainty evidence), and intranasal dexmedetomidine (MD 2.80, 95% CI 0.77 to 4.83; 1 study, moderate-certainty evidence). Children who received oral chloral hydrate appeared significantly less likely to complete neurodiagnostic procedure with child awakening when compared with rectal sodium thiopental (RR 0.95, 95% CI 0.83 to 1.09; 1 study; moderate-certainty evidence). Chloral hydrate was associated with a higher risk of the following adverse events: desaturation versus rectal sodium thiopental (RR 5.00, 95% 0.24 to 102.30; 1 study), unsteadiness versus intranasal dexmedetomidine (MD 10.21, 95% CI 0.58 to 178.52; 1 study), vomiting versus intranasal dexmedetomidine (MD 10.59, 95% CI 0.61 to 185.45; 1 study) (low-certainty evidence for aforementioned three outcomes), and crying during administration of sedation versus intranasal dexmedetomidine (MD 1.39, 95% CI 1.08 to 1.80; 1 study, moderate-certainty evidence). Chloral hydrate was associated with a lower risk of the following: diarrhoea compared with rectal sodium thiopental (RR 0.04, 95% CI 0.00 to 0.72; 1 study), lower mean diastolic blood pressure compared with sodium thiopental (MD 7.40, 95% CI 5.11 to 9.69; 1 study), drowsiness compared with oral clonidine (RR 0.44, 95% CI 0.30 to 0.64; 1 study), vertigo compared with oral clonidine (RR 0.15, 95% CI 0.01 to 2.79; 1 study) (moderate-certainty evidence for aforementioned four outcomes), and bradycardia compared with intranasal dexmedetomidine (MD 0.17, 95% CI 0.05 to 0.59; 1 study; high-certainty evidence). No other adverse events were significantly associated with chloral hydrate, although there was an increased risk of combined adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study; low-certainty evidence). AUTHORS' CONCLUSIONS: The certainty of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine. Sedation failure was similar between groups for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. Oral chloral hydrate had a higher sedation failure rate when compared with intravenous pentobarbital, rectal sodium thiopental, and music therapy. Chloral hydrate appeared to be associated with higher rates of adverse events than intranasal dexmedetomidine. However, the evidence for the outcomes for oral chloral hydrate versus intravenous pentobarbital, rectal sodium thiopental, intranasal dexmedetomidine, and music therapy was mostly of low certainty, therefore the findings should be interpreted with caution. Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for an additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially for major adverse effects such as oxygen desaturation.

Vitamin D deficiency and insufficiency in Malaysian children with spina bifida.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To determine the prevalence and potential risk factors of vitamin D deficiency and insufficiency among Malaysian children with spina bifida. SETTING: Four Malaysian tertiary hospitals. METHODS: Children with spina bifida were assessed for potential demographic, disease severity and lifestyle risk factors for vitamin D deficiency and insufficiency. Blood for 25-hydroxy vitamin D (25(OH)D) was taken. Vitamin D deficiency was defined as 25(OH)D levels ≤ 37.5 nmol/L and insufficiency as 37.6-50 nmol/L. RESULTS: Eighty children aged 2-18 years (42 males) participated in the study. Vitamin D levels ranged from 14 to 105 nmol/L (mean 52.8, SD 19.1). Vitamin D deficiency was identified in 18 (22.5%) and insufficiency in 26 (32.5%) children. Logistic regression analysis showed that skin exposure to sunlight ≤ 21% body surface area (OR: 6.2, CI 1.7-22.9) and duration of sun exposure ≤ 35 min/day (OR: 4.0, CI 1.2-14.1) were significant risk factors for vitamin D deficiency and insufficiency, respectively. CONCLUSIONS: Over half (55%) of Malaysian children with spina bifida seen in urban tertiary hospitals have vitamin D insufficiency and deficiency. Lifestyle sun exposure behaviours were risk factors for vitamin D deficiency and insufficiency.

Improving awareness, knowledge, and attitude among Malaysian parents of children with epilepsy using an Interactive Animated Epilepsy Education Programme (IAEEP).

BACKGROUND: An information technology (IT)-based epilepsy educational program, the Interactive Animated Epilepsy Education Programme (IAEEP), can potentially help improve awareness, knowledge, and attitude (AKA) of parents of children with epilepsy (CWE) enabling CWE to lead a normal life. Our study aimed to assess the following: i) baseline level of epilepsy AKA of Malaysian parents of CWE and explore potential characteristics associated with low levels of AKA; ii) effectiveness of the IAEEP in improving parental AKA, and whether these effects remained stable over time; and iii) effects of the IAEEP on parental mental state and perception of their child's quality of life. METHODS: This prospective study includes parents of CWE aged 8-18 years old with no comorbidities. Epilepsy education was delivered using the IAEEP. Parents completed an AKA questionnaire before (time point 1 [TP1]), immediately after (TP2), and 4-6 months (TP3) after the provision of IAEEP. Parent proxy report of Health-Related Quality of Life Measurement for Children with Epilepsy (CHEQOL)-25 questionnaire and Depression, Anxiety, and Stress Scale (DASS)-21 questionnaire was completed at TP1 and TP3. RESULTS: A total of 78 parents participated in the study. At baseline (TP1), parental responses were rated as "moderate" for awareness domain, "high" for knowledge domain, "very positive" for attitude domain, and "good" for total AKA score domain. No epilepsy or parental characteristics were associated with the low baseline parental AKA levels. After IAEEP intervention, there was a significant increase in all AKA subdomain scores. Post-IAEEP, the AKA of parents were rated as "very high" for awareness domain, "very high" for knowledge domain, "very positive" for attitude domain, and "excellent" for total AKA domain at both TP2 and TP3. Parent proxy CHEQOL-25 report showed significant increments in interpersonal/social and secrecy scale scores between TP1 and TP3. There were no significant differences in the DASS-21 scores between TP1 and TP3. CONCLUSION: The IAEEP is an effective epilepsy educational tool to increase the levels of AKA among parents of CWE. Following the use of the IAEEP, parents of CWE also reported an improvement of their child's quality of life in the interpersonal/social and epilepsy secrecy CHEQOL-25 domains. There was no impact on parental mental health following exposure to the IAEEP.

Quality of life in Malaysian children with epilepsy.

BACKGROUND: Children with epilepsy (CWE) are at risk of impaired quality of life (QOL), and achieving a good QOL is an important treatment goal among CWE. To date, there are no published multiethnic QOL studies in Asia. Our study aimed to: i) investigate the QOL of multiethnic CWE in Malaysia as reported by both the child and parent; ii) determine the level of agreement between child-self report and parent-proxy report QOL; and iii) explore potential correlates of sociodemographic, epilepsy characteristics, and family functioning with QOL in CWE. METHODS: Cross-sectional study of all CWE aged 8-18years old with at least 6months' duration of epilepsy, minimum reading level of primary school education Year 1, and attending mainstream education. Quality of life was measured using the parent-proxy and child self-report of Quality of Life Measurement for Children with Epilepsy (CHEQOL-25) questionnaire. Total and subscale CHEQOL-25 scores were obtained. The levels of parent-child agreement were determined using intraclass correlation coefficients (ICC). Family functioning was assessed using the General functioning subscale (GF-12). RESULTS: A total of 115 CWE and their parents participated in the study. In general, Malaysian parents rated children's total CHEQOL-25 scores poorer than the children themselves [mean total parent score: 68.56 (SD: 10.86); mean total child score: 71.82 (SD: 9.55)]. Agreement between child and parent on the CHEQOL-25 was poor to moderate (ICC ranged from 0.31-0.54), with greatest discordance in the epilepsy secrecy domain (ICC=0.31, p=0.026). Parent and child were more likely to agree on more external domains: intrapersonal/social (ICC=0.54, p<0.001) and interpersonal/emotional (ICC=0.50, p<0.001). Malay ethnicity, focal seizure and high seizure frequency (≥1 seizure per month) were associated with lower CHEQOL-25 scores. There was a significant but weak correlation between GF-12 and parent-proxy CHEQOL-25 Total Scores (r=-0.186, p=0.046). CONCLUSION: Our results emphasize the importance to have the child's perspective of their QOL as the level of agreement between the parent and child reported scores were poor to moderate. Malaysian CWE of Malay ethnicity, those with focal seizures or high seizure frequency are at risk of poorer QOL.

Vincristine-induced peripheral neuropathy in survivors of childhood acute lymphoblastic leukaemia.

BACKGROUND: Vincristine, an essential component of childhood acute lymphoblastic leukaemia (ALL) therapeutic protocols, is associated with dose-dependent neurotoxicity, but its long-term morbidity in treated children has not been clearly elucidated. The aim of this study is to determine the prevalence of vincristine-induced peripheral neuropathy (VIPN) among Malaysian childhood ALL survivors and its impact on motor function and quality of life. PROCEDURE: Survivors of childhood ALL aged 4-18 years who had completed chemotherapy for 2 years or more were evaluated for VIPN using both the clinical Total Neuropathy Score (cTNS) and nerve conduction studies. Motor function and quality of life of the survivors were assessed via the Bruininks-Oseretsky Test of Motor Proficiency Brief Form, Second Edition (BOT-2 Brief Form) and the Paediatric Quality of Life version 4.0 Generic Core Scales (PedsQL4.0) questionnaire, respectively. RESULTS: One hundred and one survivors with a duration of follow-up ranging from 2.0 to 10.3 years were recruited. Twenty-seven (26.7%) had abnormal cTNS scores and 69 (68.3%) had electrophysiological evidence of neuropathy. Of these, 16 (15.8%) had combined clinical and electrophysiological neuropathy (VIPN). Those previously treated on the intermediate- or high-risk treatment stratification arms had a higher risk of developing VIPN (67.3 vs. 32.7%; odds ratio [OR]: 9.06, 95% confidence interval [CI]: 1.14-71.86; P = 0.014). Survivors with VIPN had significantly lower quality of life scores in the physical (P = 0.024) and social domains (P = 0.039) compared with peers without VIPN, but no association with poorer motor function was observed. CONCLUSIONS: Sixteen percent of ALL survivors had VIPN. VIPN should be increasingly recognised as a late effect of chemotherapy, as it significantly affects physical and social function quality of life.

Provision of sudden unexpected death in epilepsy (SUDEP) information among Malaysian parents of children with epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is an important cause of mortality in epilepsy. To date, there is only one published UK study evaluating information provision of SUDEP among parents of children with epilepsy (CWE), and there are no studies published from Asia. Although SUDEP information provision is recommended among parents of CWE, it is uncertain if these recommendations are applicable to Asian countries due to the different cultural attitude towards epilepsy. Our prospective cohort study consisted of multiethnic parents of children with epilepsy (CWE) seen in a tertiary hospital in Malaysia. Information on SUDEP was delivered to parents using an epilepsy educational software program. Participants completed a set of standardized questionnaire and Depression Anxiety Stress Scales-Short Form (DASS-21) immediately after and retested 3-6months after the SUDEP information provision. A total of 127 parents (84 mothers) participated in the study. The CWE consisted of 3 ethnic groups (38% Malay, 30% Chinese, 32% Indian) with a mean age of 9.6years. Majority (70.9%) felt positive after SUDEP information provision, 90.6% wanted SUDEP discussion for themselves with 70.1% wanted SUDEP discussion with their child, and a lower proportion (58.3%) would discuss SUDEP with their child. None of the participants reported increased symptoms of depression, stress or anxiety attributed to SUDEP information provision. Most parents took steps to reduce SUDEP risk, and most parents did not report an impact on their own functioning. However, there was an increase in parental report over time of impact on their child's functioning following SUDEP information (P<0.05). In conclusion, most Malaysian parents of CWE wanted SUDEP information. Following SUDEP information disclosure, majority did not report negative emotions; however, an increase in parents over time reported an impact on their child. Our findings reiterate that provision of SUDEP information should form part of care of CWE and parents should receive ongoing support as they undergo a period of parenting adjustment when dealing with the information provided.

Chloral hydrate as a sedating agent for neurodiagnostic procedures in children.

BACKGROUND: Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure. OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children. SEARCH METHODS: We used the standard search strategy of the Cochrane Epilepsy Group. We searched MEDLINE (OVID SP) (1950 to July 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 7, 2017), Embase (1980 to July 2017), and the Cochrane Epilepsy Group Specialized Register (via CENTRAL) using a combination of keywords and MeSH headings. SELECTION CRITERIA: We included randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo for children undergoing non-invasive neurodiagnostic procedures. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data, mean difference (MD) for continuous data, with 95% confidence intervals (CIs). MAIN RESULTS: We included 13 studies with a total of 2390 children. The studies were all conducted in hospitals that provided neurodiagnostic services. Most studies assessed the proportion of sedation failure during the neurodiagnostic procedure, time for adequate sedation, and potential adverse effects associated with the sedative agent.The methodological quality of the included studies was mixed, as reflected by a wide variation in their 'Risk of bias' profiles. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 13 studies had high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in single small studies.Children who received oral chloral hydrate had lower sedation failure when compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study, moderate-quality evidence). Children who received oral chloral hydrate had a higher risk of sedation failure after one dose compared to those who received intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study, low-quality evidence), but after two doses there was no evidence of a significant difference between the two groups (RR 3.00, 95% CI 0.33 to 27.46; 1 study, very low-quality evidence). Children who received oral chloral hydrate appeared to have more sedation failure when compared with music therapy, but the quality of evidence was very low for this outcome (RR 17.00, 95% CI 2.37 to 122.14; 1 study). Sedation failure rates were similar between oral chloral hydrate, oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam.Children who received oral chloral hydrate had a shorter time to achieve adequate sedation when compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study, moderate-quality evidence), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study, moderate-quality evidence), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study, moderate-quality evidence), and rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study, low-quality evidence) and intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study, moderate-quality evidence).No data were available to assess the proportion of children with successful completion of neurodiagnostic procedure without interruption by the child awakening. Most trials did not assess adequate sedation as measured by specific validated scales, except in the comparison of chloral hydrate versus intranasal midazolam and oral promethazine.Compared to dexmedetomidine, chloral hydrate was associated with a higher risk of nausea and vomiting (RR 12.04 95% CI 1.58 to 91.96). No other adverse events were significantly associated with chloral hydrate (including behavioural change, oxygen desaturation) although there was an increased risk of adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study, low-quality evidence). AUTHORS' CONCLUSIONS: The quality of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was very variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine for children undergoing paediatric neurodiagnostic procedures. The sedation failure was similar for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. When compared with intravenous pentobarbital and music therapy, oral chloral hydrate had a higher sedation failure rate. However, it must be noted that the evidence for the outcomes for the comparisons of oral chloral hydrate against intravenous pentobarbital and music therapy was of very low to low quality, therefore the corresponding findings should be interpreted with caution.Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially the risk of major adverse effects such as bradycardia, hypotension, and oxygen desaturation.

Vitamin D deficiency and its risk factors in Malaysian children with epilepsy.

OBJECTIVE: Long-term use of antiepileptic drugs (AEDs) is a significant risk factor for vitamin D deficiency in children with epilepsy. The aims of our study were to evaluate the prevalence and risk factors for vitamin D deficiency among Malaysian children with epilepsy. METHODS: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in three tertiary hospitals in Malaysia from April 2014 to April 2015. Detailed assessment of pubertal status, skin pigmentation, sunshine exposure behavior, physical activity, dietary vitamin D and calcium intake, anthropometric measurements and bone health blood tests (vitamin D, alkaline phosphatase, calcium, phosphate, and parathyroid hormone levels) were obtained on all patients. Vitamin D deficiency was defined as 25-hydroxy vitamin D [25(OH)D] levels ≤35 nmol/L and insufficiency as 25(OH)D levels of 36-50 nmol/L. RESULTS: A total of 244 children (146 male) participated in the study. Ages ranged between 3.7 and 18.8 years (mean 12.3 years). 25(OH)D levels ranged between 7.5 and 140.9 nmol/L (mean 53.9 nmol/L). Vitamin D deficiency was identified in 55 patients (22.5%), and a further 48 (19.7%) had vitamin D insufficiency. Multivariate logistic regression analysis identified polytherapy >1 AED (odds ratio [OR] 2.16, 95% confidence interval [CI] 1.07-4.36), age >12 years (OR 4.16, 95% CI 1.13-15.30), Indian ethnicity (OR 6.97, 95% CI 2.48-19.55), sun exposure time 30-60 min/day (OR 2.44, 95% CI 1.05-5.67), sun exposure time <30 min/day (OR 3.83, 95% CI 1.61-9.09), and female (OR 2.61, 95% CI 1.31-5.20) as statistically significant (p < 0.05) risk factors for vitamin D deficiency. SIGNIFICANCE: Despite living in the tropics, a high proportion of Malaysian children with epilepsy are at risk of vitamin D deficiency. Targeted strategies including vitamin D supplementation and lifestyle advice of healthy sunlight exposure behavior should be implemented among children with epilepsy, particularly for those at high risk of having vitamin D deficiency.

RORA gene rs12912233 and rs880626 polymorphisms and their interaction with SCN1A rs3812718 in the risk of epilepsy: a case-control study in Malaysia.

RAR-related orphan receptors A (RORA) and B (RORB) and voltage-gated sodium channel type 1 (SCN1A) genes play critical roles in the regulation of the circadian clock. Evidence has shown an association of RORA and RORB polymorphisms with susceptibility to autism and depression. Hence, we tested the association of RORA rs12912233, rs16943429, rs880626, rs2290430, and rs12900948; RORB rs1157358, rs7022435, rs3750420, and rs3903529; and SCN1A rs3812718 with epilepsy risk in the Malaysians. DNA was genotyped in 1789 subjects (39% epilepsy patients) by using MassARRAY (Sequenom). Significant association was obtained for rs12912233 in Malaysian Chinese (p=0.003). Interaction between rs12912233-rs880626 and rs3812718 was associated with the epilepsy risk in the subjects overall (p=0.001). Results show that RORA rs12912233 alone might be a possible risk variant for epilepsy in Malaysian Chinese, but that, together with RORA rs880626 and SCN1A rs3812718, this polymorphism may have a synergistic effect in the epilepsy risk in Malaysians.

Variable outcome for epilepsy after neonatal hypoglycaemia.

AIM: To evaluate the electroclinical features of epilepsy secondary to neonatal hypoglycaemia. METHOD: This was a retrospective study of children who had seizures beyond infancy after neonatal hypoglycaemia treated at The Royal Children's Hospital, Melbourne between 1996 and 2012. Patients with perinatal asphyxia were excluded. Clinical details were obtained from medical records. Digital electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were reviewed. Eleven patients met the inclusion criteria (six males, five females; mean age 10y 5mo, range 4-18y at the time of review). RESULTS: Age at seizure onset ranged from 4 months to 5 years. Seizures were focal occipital in nine and generalized tonic in two patients. MRI showed gliosis with or without cortical atrophy in the occipital lobe with or without parietal lobe in all. Predominant EEG findings were stereotyped occipital sharp-slow discharges in five, polymorphic occipital spike-wave or paroxysmal fast activity in three, and generalized slow spike-wave and fast activity in two. Seizures were infrequent or remitted in six of the nine children with focal occipital seizures, and frequent and refractory in both children with generalized seizures. INTERPRETATION: Despite the common antecedent and bilateral occipital lobe injury, the seizure manifestations and course of epilepsy after neonatal hypoglycaemia were variable, with mild occipital, refractory occipital, and symptomatic generalized epilepsy recognized.

An investigation into the relationship between vigabatrin, movement disorders, and brain magnetic resonance imaging abnormalities in children with infantile spasms.

AIM: We aimed to investigate the relationship between movement disorders, changes on brain magnetic resonance imaging (MRI), and vigabatrin therapy in children with infantile spasms. METHOD: Retrospective review and brain MRI analysis of children enrolled in the International Collaborative Infantile Spasms Study (ICISS) who developed a movement disorder on vigabatrin therapy. Comparisons were made with controls within ICISS who had no movement disorder. RESULTS: Ten of 124 infants had a movement disorder and in eight it had developed on vigabatrin therapy. Two had a movement disorder that resolved on dose-reduction of vigabatrin, one had improvement on withdrawing vigabatrin, two had resolution without any dose change, and in three it persisted despite vigabatrin withdrawal. The typical brain MRI changes associated with vigabatrin therapy were noted in two infants. Ten control infants were identified. Typical MRI changes noted with vigabatrin were noted in three controls. INTERPRETATION: It is possible that in two out of eight cases, vigabatrin was associated with the development of a movement disorder. In six out of eight cases a causal relationship was less plausible. The majority of infants treated with vigabatrin did not develop a movement disorder. MRI changes associated with vigabatrin do not appear to be specifically related to the movement disorder.

Management of status epilepticus in Malaysia: A national survey of current practice and treatment gap.

INTRODUCTION: Early and effective treatment is fundamental in status epilepticus (SE) management. At the initiative of the Epilepsy Council of Malaysia, this study aimed to determine the treatment gap in SE across different healthcare settings in Malaysia. METHODS: A web-based survey was sent to clinicians involved in the management of SE, across all states and at all levels of healthcare services. RESULTS: A total of 158 responses were received from 104 health facilities, including 23 tertiary government hospitals (95.8% of all government tertiary hospitals in Malaysia), 4 (80.0%) universities, 14 (6.7%) private, 15 (11.5%) district hospitals and 21 clinics. Intravenous (IV) diazepam was available in 14 (93.3%) district and 33 (80.5%) tertiary hospitals for prehospital management. Non-IV benzodiazepine (rectal diazepam and intramuscular midazolam) was not widely available in prehospital services (75.8% and 51.5%). Intramuscular midazolam was underutilised (60.0% in district and 65.9% in tertiary hospitals). IV sodium valproate and levetiracetam were only available in 66.7% and 53.3% of the district hospitals, respectively. Electroencephalogram (EEG) services were available in only 26.7% of the district hospitals. Non-pharmacological therapies such as ketogenic diet, electroconvulsive therapy, and therapeutic hypothermia were not available in most district and tertiary hospitals for refractory and super-refractory SE. CONCLUSIONS: We identified several gaps in the current practice of SE management, including limited availability and underutilization of non-IV midazolam in prehospital services, underutilization of non-IV midazolam and other second-line ASMs, and lack of EEG monitoring in district hospitals and limited treatment options for refractory and super-refractory SE in tertiary hospitals.

Variation in prognosis and treatment outcome in juvenile myoclonic epilepsy: a Biology of Juvenile Myoclonic Epilepsy Consortium proposal for a practical definition and stratified medicine classifications.

Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes. Our study is based on clinical data collected by the Biology of Juvenile Myoclonic Epilepsy Consortium augmented by literature data. We review prognosis research on mortality and seizure remission, predictors of antiseizure medication resistance and selected adverse drug events to valproate, levetiracetam and lamotrigine. Based on our analysis, a simplified set of diagnostic criteria for juvenile myoclonic epilepsy includes the following: (i) myoclonic jerks as mandatory seizure type; (ii) a circadian timing for myoclonia not mandatory for the diagnosis of juvenile myoclonic epilepsy; (iii) age of onset ranging from 6 to 40 years; (iv) generalized EEG abnormalities; and (v) intelligence conforming to population distribution. We find sufficient evidence to propose a predictive model of antiseizure medication resistance that emphasises (i) absence seizures as the strongest stratifying factor with regard to antiseizure medication resistance or seizure freedom for both sexes and (ii) sex as a major stratifying factor, revealing elevated odds of antiseizure medication resistance that correlates to self-report of catamenial and stress-related factors including sleep deprivation. In women, there are reduced odds of antiseizure medication resistance associated with EEG-measured or self-reported photosensitivity. In conclusion, by applying a simplified set of criteria to define phenotypic variations of juvenile myoclonic epilepsy, our paper proposes an evidence-based definition and prognostic stratification of juvenile myoclonic epilepsy. Further studies in existing data sets of individual patient data would be helpful to replicate our findings, and prospective studies in inception cohorts will contribute to validate them in real-world practice for juvenile myoclonic epilepsy management.

SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10-9) and 10p11.21 (P = 3.6 × 10-8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10-3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10-3) and increased seizure-like events (P = 6.8 × 10-7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10-3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.

Sex-specific disease modifiers in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p < 0.001). Absence seizures significantly predicted drug resistance in both males (OR = 3.0, p = 0.001) and females (OR = 3.0, p < 0.001) in univariate analysis. In multivariable analysis in females, catamenial seizures (OR = 14.7, p = 0.001), absence seizures (OR = 6.0, p < 0.001) and stress-precipitated seizures (OR = 5.3, p = 0.02) were associated with drug resistance, while a photoparoxysmal response predicted seizure freedom (OR = 0.47, p = 0.03). Females with both absence seizures and stress-related precipitants constitute the prognostic subgroup in JME with the highest prevalence of drug resistance (49%) compared to females with neither (15%) and males (29%), highlighting the unmet need for effective, targeted interventions for this subgroup. We propose a new prognostic stratification for JME and suggest a role for circuit-based risk of seizure control as an avenue for further investigation.